ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.1282C>G (p.Pro428Ala)

gnomAD frequency: 0.00001  dbSNP: rs368880414
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000569333 SCV000673461 likely benign Hereditary cancer-predisposing syndrome 2016-10-15 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae RCV001051328 SCV001215475 uncertain significance Birt-Hogg-Dube syndrome 2023-12-08 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 428 of the FLCN protein (p.Pro428Ala). This variant is present in population databases (rs368880414, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with FLCN-related conditions. ClinVar contains an entry for this variant (Variation ID: 485600). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt FLCN protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV001755957 SCV002006907 uncertain significance not provided 2022-12-02 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.